# Severe neonatal cholestasis in HNF1β deficiency: a case report and literature review

## TL;DR

A newborn with severe cholestasis and multiple abnormalities was found to have a genetic deletion involving the HNF1β gene, which was successfully treated with hormone therapy.

## Contribution

This case highlights the link between HNF1β gene deletion and neonatal cholestasis with hypopituitarism, emphasizing the importance of early genetic testing.

## Key findings

- Cholestasis resolved rapidly with hormone therapy in a neonate with HNF1β deficiency.
- A de novo 17q12 deletion involving HNF1β was identified as the cause of the complex clinical phenotype.
- The case underscores the need for prompt endocrine and genetic evaluation in neonatal cholestasis.

## Abstract

Neonatal cholestasis can be caused by several conditions, with biliary atresia being the major cause. Genetic and endocrinological etiologies represent other possibilities, with most of them requiring a rapid diagnosis and a specific treatment. We describe a neonatal case of severe cholestasis with low gamma glutamyl transferase in a child presenting with multiple abnormalities, including pituitary stalk interruption syndrome and consequent hypopituitarism. The cholestasis was rapidly resolved with hormone therapy. Genetic analysis showed a de novo 17q chromosome deletion, including the HNF1β gene implicated in liver damage, and this was considered causative of the complex clinical phenotype. Our case highlights the relationship between congenital hypopituitarism and HNF1β gene deletion in 17q12 deletion syndrome as a severe neonatal cholestasis etiology, emphasizing the need to be especially vigilant in cases with associated hypoglycemia. Prompt endocrine evaluation and genetic testing are crucial in neonatal cholestasis to start targeted therapy and long-term monitoring, which could mitigate serious complications.